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Posttranslational modification of histone 1.4 by SET7/9 and ARTD1


Barandun, Marc André. Posttranslational modification of histone 1.4 by SET7/9 and ARTD1. 2014, University of Zurich, Vetsuisse Faculty.

Abstract

Proteins are important for the regulation of biochemical processes and are crucial for the structure and function of cells. Proteins are post-translationally often chemically modified, which regulates their function and enzymatic activities. The work presented in this thesis shows that the mono-methyltransferase SET7/9 modifies the linker histone H1.4 only at the C-terminal domain. Several lysine residues (K121, K129, K159, K171, K177 and K192) were identified to be methylated. SET7/9 only modified lysine residues at the terminal position of a given KAK motif. Also, the addition of DNA to the methylation reaction inhibited the modification of H1.4 by SET7/9. Expression analysis of GFP-tagged full length H1.4 or its C-terminal or N- terminal fragments in U2OS cells suggested that all fusion proteins localize to either hetero- or euchromatin in the nucleus. Furthermore, the ADP-ribosyltransferase ARTD1 modified several amino acid residues in the C-terminal domain of H1.4, a process that inhibited SET7/9-dependent methylation. This mutual exclusion of the two modifications suggests that post- translational modification of structurally close amino acids can influence each other and thereby regulate the functionality of proteins.

Keywords: H1.4, SET7/9, ARTD1

Abstract

Proteins are important for the regulation of biochemical processes and are crucial for the structure and function of cells. Proteins are post-translationally often chemically modified, which regulates their function and enzymatic activities. The work presented in this thesis shows that the mono-methyltransferase SET7/9 modifies the linker histone H1.4 only at the C-terminal domain. Several lysine residues (K121, K129, K159, K171, K177 and K192) were identified to be methylated. SET7/9 only modified lysine residues at the terminal position of a given KAK motif. Also, the addition of DNA to the methylation reaction inhibited the modification of H1.4 by SET7/9. Expression analysis of GFP-tagged full length H1.4 or its C-terminal or N- terminal fragments in U2OS cells suggested that all fusion proteins localize to either hetero- or euchromatin in the nucleus. Furthermore, the ADP-ribosyltransferase ARTD1 modified several amino acid residues in the C-terminal domain of H1.4, a process that inhibited SET7/9-dependent methylation. This mutual exclusion of the two modifications suggests that post- translational modification of structurally close amino acids can influence each other and thereby regulate the functionality of proteins.

Keywords: H1.4, SET7/9, ARTD1

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Additional indexing

Item Type:Dissertation (monographical)
Referees:Hottiger Michael O, Naegeli Hanspeter
Communities & Collections:05 Vetsuisse Faculty > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease

UZH Dissertations
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Place of Publication:Zürich
Date:2014
Deposited On:28 Apr 2019 15:08
Last Modified:15 Apr 2021 15:03
Number of Pages:87
OA Status:Green

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